U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C20H21FN2O
Molecular Weight 324.3919
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CITALOPRAM

SMILES

CN(C)CCCC1(OCC2=C1C=CC(=C2)C#N)C3=CC=C(F)C=C3

InChI

InChIKey=WSEQXVZVJXJVFP-UHFFFAOYSA-N
InChI=1S/C20H21FN2O/c1-23(2)11-3-10-20(17-5-7-18(21)8-6-17)19-9-4-15(13-22)12-16(19)14-24-20/h4-9,12H,3,10-11,14H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C20H21FN2O
Molecular Weight 324.3919
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

Citalopram (brand names: Celexa, Cipramil, and others) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class. It has U.S. Food and Drug Administration approval to treat major depression,[2]which it received in 1998, and is prescribed off-label for other conditions. In Australia, the UK, Germany, Portugal, Poland, and most European countries, it is licensed for depressive episodes and panic disorder with or without agoraphobia. In Spain, it is also used for obsessive-compulsive disorder. Citalopram HBr is a racemic bicyclic phthalane derivative designated (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5carbonitrile, HBr. The mechanism of action of citalopram HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). In vitro and in vivo studies in animals suggest that citalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. The single-and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10-60 mg/day. Biotransformation of citalopram is mainly hepatic, with a mean terminal half-life of about 35 hours.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.78 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CELEXA
Primary
Celexa

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 ng/mL
20 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
8.5 ng/mL
60 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
6.1 ng/mL
40 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
21.7 ng/mL
20 mg single, oral
CITALOPRAM plasma
Homo sapiens
43.7 ng/mL
40 mg single, oral
CITALOPRAM plasma
Homo sapiens
65.6 ng/mL
60 mg single, oral
CITALOPRAM plasma
Homo sapiens
10.6 ng/mL
10 mg single, oral
CITALOPRAM plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
204.5 ng × h/mL
20 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
1153.2 ng × h/mL
60 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
843.7 ng × h/mL
40 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
1010.4 ng × h/mL
20 mg single, oral
CITALOPRAM plasma
Homo sapiens
2070.3 ng × h/mL
40 mg single, oral
CITALOPRAM plasma
Homo sapiens
2946.5 ng × h/mL
60 mg single, oral
CITALOPRAM plasma
Homo sapiens
533.2 ng × h/mL
10 mg single, oral
CITALOPRAM plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
77.5 h
60 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
79.3 h
40 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
38.5 h
20 mg single, oral
CITALOPRAM plasma
Homo sapiens
40 h
40 mg single, oral
CITALOPRAM plasma
Homo sapiens
39.5 h
60 mg single, oral
CITALOPRAM plasma
Homo sapiens
36.3 h
10 mg single, oral
CITALOPRAM plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
26%
20 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
26%
60 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
26%
40 mg single, oral
DESMETHYLCITALOPRAM plasma
Homo sapiens
18%
20 mg single, oral
CITALOPRAM plasma
Homo sapiens
18%
40 mg single, oral
CITALOPRAM plasma
Homo sapiens
18%
60 mg single, oral
CITALOPRAM plasma
Homo sapiens
18%
10 mg single, oral
CITALOPRAM plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
Initial Treatment Celexa (citalopram HBr) should be administered at an initial dose of 20 mg once daily, with an increase to a maximum dose of 40 mg/day at an interval of no less than one week. Doses above 40 mg/day are not recommended due to the risk of QT prolongation. Additionally, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose. Special Populations 20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age, patients with hepatic impairment, and for CYP2C19 poor metabolizers or those patients taking cimetidine or another CYP2C19 inhibitor.
Route of Administration: Oral
In Vitro Use Guide
It was investigated the mechanisms of cytotoxic effects of in vitro and in vivo citalopram treatment on liver and the following cytolethal events. For in vitro experiments, freshly isolated rat hepatocytes were exposed to citalopram along with/without various agents. In the in vitro experiments, citalopram (500 µM) exposure demonstrated cell death, a marked elevation in ROS formation, mitochondrial potential collapse, lysosomal membrane leakiness, glutathione (GSH) depletion and lipid peroxidation. In vivo biochemistry panel assays for liver enzymes function (AST, ALT and GGTP) and histological examination confirmed citalopram (20 mg/kg)-induced damage. Citalopram-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, MPT pore sealing agents, endocytosis inhibitors, ATP generators and CYP inhibitors.
Substance Class Chemical
Record UNII
0DHU5B8D6V
Record Status Validated (UNII)
Record Version